Padigel Udaikumar M, Lee James J, Nolan Thomas J, Schad Gerhard A, Abraham David
Department of Microbiology and Immunology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.
Infect Immun. 2006 Jun;74(6):3232-8. doi: 10.1128/IAI.02067-05.
Several studies have demonstrated roles for eosinophils during innate and adaptive immune responses to helminth infections. However, evidence that eosinophils are capable of initiating an immune response to parasite antigens is lacking. The goal of the present in vitro study was to investigate the potential of eosinophils to serve as antigen-presenting cells (APC) and initiate an immune response to parasite antigens. Purified eosinophils were exposed to soluble Strongyloides stercoralis antigens, and the expression of various surface markers involved in cell activation was examined. Antigen-exposed eosinophils showed a sixfold increase in expression levels of CD69 and major histocompatibility complex (MHC) class II, a fourfold increase in levels of T-cell costimulatory molecule CD86, and a twofold decrease in levels of CD62L compared to eosinophils cultured in medium containing granulocyte-macrophage colony-stimulating factor. The ability of eosinophils to present antigen to T cells was determined by culturing them with T cells in vitro. Eosinophils pulsed with antigen stimulated antigen-specific primed T cells and CD4+ T cells to increase interleukin-5 (IL-5) production. The blocking of MHC class II expression on eosinophils inhibited their ability to induce IL-5 production by CD4+ T cells in culture. Antigen-pulsed eosinophils were able to prime naïve T cells and CD4+ T cells in culture and polarized them into Th2 cells producing IL-5 similar to that induced by antigen-loaded dendritic cells. These results demonstrate that eosinophils are capable of activating antigen-specific Th2 cells inducing the release of cytokines and assist in the priming of naïve T cells to initiate Th2 responses against infection. This study highlights the potential of eosinophils to actively induce immune responses against infection by amplifying antigen-specific Th2-cell responses.
多项研究已证明嗜酸性粒细胞在针对蠕虫感染的固有免疫和适应性免疫反应中发挥作用。然而，缺乏嗜酸性粒细胞能够启动针对寄生虫抗原的免疫反应的证据。本体外研究的目的是调查嗜酸性粒细胞作为抗原呈递细胞（APC）并启动针对寄生虫抗原的免疫反应的潜力。将纯化的嗜酸性粒细胞暴露于可溶性粪类圆线虫抗原，并检测参与细胞活化的各种表面标志物的表达。与在含有粒细胞-巨噬细胞集落刺激因子的培养基中培养的嗜酸性粒细胞相比，暴露于抗原的嗜酸性粒细胞的CD69和主要组织相容性复合体（MHC）II类的表达水平增加了六倍，T细胞共刺激分子CD86的水平增加了四倍，而CD62L的水平降低了两倍。嗜酸性粒细胞向T细胞呈递抗原的能力通过在体外将它们与T细胞共培养来确定。用抗原脉冲处理的嗜酸性粒细胞刺激抗原特异性致敏T细胞和CD4+ T细胞以增加白细胞介素-5（IL-5）的产生。阻断嗜酸性粒细胞上MHC II类的表达会抑制它们在培养物中诱导CD4+ T细胞产生IL-5的能力。抗原脉冲处理的嗜酸性粒细胞能够在培养物中激活幼稚T细胞和CD4+ T细胞，并将它们极化为产生IL-5的Th2细胞，类似于由负载抗原的树突状细胞诱导的情况。这些结果表明，嗜酸性粒细胞能够激活抗原特异性Th2细胞，诱导细胞因子的释放，并协助幼稚T细胞的启动，以引发针对感染的Th2反应。本研究突出了嗜酸性粒细胞通过放大抗原特异性Th2细胞反应来积极诱导针对感染的免疫反应的潜力。
